The present invention relates to improvements in the use of hollow fibers for immobilization of whole cells and the like.
Several techniques are known in the art for immobilization of whole cells for purposes such as extended fermentation. These include surface attachment, entrapment within porous matrices, self aggregation and containment behind a barrier. See, for example, I. Chibata, "Immobilized Enzymes--Research and Development", Kodansha, Tokyo, Japan (1978); K. Venkatasubramanian, Desalination, 35; 353 (1980); A. M. Klibanov, Science, 219:722 (1983); S. F. Karel et al., Chem. Eng. Sci., 40: 1321-1354 (1985).
Of particular interest is the use of hollow fiber immobilization systems. Such systems use continuous lengths of hollow fibers whose ends are potted in tube sheets. In such systems, the cells may be entrapped in the fiber lumen with substrate solution flowing on the shell side of the device. Alternatively, the cells are entrapped on the shell side (the extra capillary space) and substrate solution flows generally through the fiber lumen. Higher cell densities, maintenance of cell viability for extended periods, continuous removal of product and inhibitory wastes, isolation of cells from the main substrate stream, and higher volumetric productivities are major advantages for such devices.
Applications include yeast immobilization (D. S. Inloes et al., Appl. Environ. Microbiol., 46: 264 (1983)); plant cell immobilization (M. L. Shuler, Ann. N.Y. Acad. Sci., 369: 65 (1981); J. E. Prenosil et al., Enzyme Microb. Technol., 5: 323 (1983)) and animal cell entrapment (W. L. Chick et al., Science, 197: 780 (1979)).
However, presently available hollow fiber devices have several limitations. Hollow fiber walls tend to rupture because of uncontrolled cell growth. There are also limitations on diffusion through the fibers as well as problems relating to membrane leakage, gas supply and removal of products and wastes. See, for example, D. S. Inloes et al., Appl. Environ. Microbiol., 46: 264-278 (1983).